Background: Irritable Bowel Syndrome (IBS) is a common chronic gastrointestinal (Gl) disorder defined by recurrent symptoms of abdominal pain or discomfort associated with alterations in bowel habits, in the absence of a detectable organic cause. Though many IBS patients have extraintestinal symptoms, these are generally not considered under the conventional paradigm. Partly from the lack of effective therapies, 30- 40% of IBS patients turn to complementary and alternative medical (CAM) therapies instead of, or in addition to, conventional treatment. Unlike the western approach, Traditional Chinese Medicine (TCM) views IBS patients as a heterogeneous population whose Gl symptoms are one of many manifestations resulting from a broader underlying multisystemic dysregulation. In TCM patterns of dysregulation, patients are classified into subgroups incorporating both Gl and extraintestinal symptoms. TCM therapies like acupuncture and herbs target these specific patterns. Further, TCM patterns show striking similarity to common presentations of IBS and to emerging concepts of stress neurobiology, particularly allostasis and allostatic load. Despite its core role in the TCM paradigm, few studies explore the nature of patterns of dysregulation. Aims: Building on extensive preliminary data, this proposal seeks to scientifically validate TCM patterns by testing the following hypotheses: 1) TCM patterns can be characterized by distinct pathophysiologic patterns related to specific alterations in stress responsiveness, and 2) TCM patterns can be distinguished by select symptom items. Methods: In Aim 1, we will assess affective, pain, autonomic and neuroendocrine responses to visceral and somatic pain stimuli to identify two distinct patterns (EXCESS and DEFICIENCY) reflecting altered stress responsiveness (allostasis and allostatic load, respectively). In Aim 2, we will assess correlation between patient self-report of select symptom items and TCM expert diagnosis of patients to specific TCM patterns. Conclusions: If these hypotheses are correct, it strongly validates the existence of TCM patterns of dysregulation in IBS, supports that IBS is a heterogeneous, multisystemic disorder contrary to current characterizations, and provides the basis for novel diagnostic and treatment approaches. Given the disappointing results with conventional approaches to multisystemic functional disorders like IBS, this may provide exciting insights and contributions to the classification and treatment of these challenging disorders. [unreadable] [unreadable] [unreadable]